Molecular Mechanisms Leading to Macrophage Activation
Because of their potent microbicidal and tumoricidal capacities, macrophages play a major role in the immune response. Macrophage functions are not constitutive, being rather acquired (activation) in the presence of molecules such as cytokines or microbial-derived products. Binding of these molecules at the surface of a resting macrophage triggers intracellular signalling pathways, leading to the induction of gene expression and protein synthesis. These intracellular events culminate in the acquisition of phenotypes allowing the macrophage to perform specific immune functions.
One of my objectives is to gain a better knowledge of the molecular mechanisms leading to macrophage activation. This is essential for the development of novel pharmacological approaches based on the selective manipulation of intracellular signalling pathways. Currently, we are concentrating our efforts on the role of a family of closely related serine/threonine kinases known as protein kinase C (PKC). We are interested in determining to which extent individual PKC isoenzymes regulate (i) macrophage responses to microbial-derived molecules and (ii) phagocytosis.
Molecular Interaction Between Leishmania and the Macrophage
We also investigate the interaction between the intracellular parasite Leishmania and the macrophage. Although the inside of a macrophage seems inhospitable, several intracellular microbes chose the macrophage as a host cell. Of course, these microbes evolved strategies to avoid or manipulate host immune defenses. One of these strategies consists in modulating in their favor their host cell intracellular signalling pathways. Since Leishmania interferes with macrophage activation through inhibition of PKCs, studying the underlying mechanisms will enhance our understanding of macrophage function regulation.
In the macrophage, Leishmania resides within a phagolysosomal vacuole. Using genetically defined Leishmania virulence mutants, we have shown that this parasite can modulate the biogenesis of their vacuole using surface glycolipids. Defining the molecular composition of vacuoles induced by virulence mutants will contribute to our understanding of basic microbial pathogenesis problems.
Dr. Albert Descoteaux obtained his B.Sc. (Biological Sciences, 1984) and M.Sc. (Microbiology, 1987) degrees from Université de Montréal, and his Ph.D. degree (Parasitology, 1991) from McGill University. After post-doctoral training at the University of Kentucky (1991-1993) and at Harvard Medical School (1993-1995), he became Assistant Professor at the McGill Centre for the Study of Host Resistance. He is also currently Adjunct Professor within the Department of Microbiology and Immunology of the McGill University.
Dans les médias
// 6 août 2013
// 29 juillet 2013
// 16 septembre 2011
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